The primary objective of the laboratory is the study of protease regulation in the circulation, a process primarily mediated by binding of protease to inhibitors followed by clearance from the circulation. Studies this year have involved clearance of (1) alpha-macroglobulin (alpha 2-M) complexes with trypsin, thrombin and plasmin as well as with methylamine (MeNH2) which alters alpha 2-M in a manner analogous to proteases; (2) antithrombin III (At III) complexes with thrombin. Moreover, during the current year, the laboratory has begun studying the in vitro binding of alpha 2-M complexes to macrophages since the route of clearance of complexes from the circulation is via the reticulo-endothelial system (RES). Recently, the applicant has begun a series of studies with cis-dichloro-diameplatinum (II) (cis-DDP) and alpha 2-M. These studies were undertaken since cis-DDP is an important antitumor drug which possesses two amine groups. It was felt that cis-DDP might react with alpha 2-M in a manner analogous to MeNH2.